Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Acute toxicity: Oral


In an acute oral toxicity study in female Wistar rats, following the acute toxic class method in a method similar to the OECD Guideline 401 (Megens; 1992), the LD50 of T001624 was established to be 85.7 mg/kg bw for males and females (LD50 males = 113 mg/kg bw; LD50 females = 65 mg/kg bw). T001624 was found to be moderately toxic by the oral route and should be classified as Category 3 according to CLP regulation (EC) No 1272/2008.


 


In an acute oral toxicity study in rats, the LD50 of T001624 was found to be 129.9 mg/kg (Janssen; 1990).


 


The studies were used in a weight-of-evidence approach. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
65.5 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity:


An acute oral toxicity study with T001624 according to a method similar to OECD TG 401 with 5 female and 5 male Wistar rats was performed by Megens (1992). The test material was formulated as aqueous suspensions at concentrations of 40, 80 and 160  mg/kg bw. The animals were observed for 14 days following administration. Mortality/viability was observed immediately after dosing,  periodically during day 1 and at least once daily until the end of the observation period. Body weight, clinical observations and gross pathology were also recorded. Necrospy of survivors and macroscopic examination were also performed.


Mortality was observed as follows: 


   - males: 1 animal at 80 mg/kg bw and 4 at 160 mg/kg bw


   - females: 4 animals at 80 mg/kg bw and 5 at 160 mg/kg bw


All deaths occurred within a period of 6 hours after administration of the test item.


The most frequent observed abnormalities were: catalepsy, hypotonia, hypothermia, sedation and tremors. All surviving animals became again normal within a period of 2 days after administration of T001624.  


The oral LD50 value of T001624 in Wistar rats was established to be 85.7 mg/kg bw for males and females (LD50 males = 113 mg/kg bw; LD50 females = 65 mg/kg bw), which classifies T001624 as Category 3 according to the CLP regulation.


 


In addition, in an acute oral toxicty study performed by Janssen (1990), T001624 was orally administered at 40, 160 and 640 mg/kg in rats (5 animals per dose). All animals died at 640 mg/kg bw, 4/5 at 160 mg/kg and none died at 40 mg/kg. The oral LD50-value of T001624 was considered to be 129.9 mg/kg.


 


In a Janssen Expert Report prepared by De Smedt and Lammens (Expert Report JNJ-17794172682820-AAC, 2015-08-12) it was concluded that based on (1) the high number of mortalities in the K1 study (9/10 after dosing at 160 mg/kg bw, 5/10 after dosing at 80 mg/kg bw, (2) the internal communication (1990) with high number of mortalities (5/5 after dosing at 640 mg/kg bw, 4/5 after dosing at 160 mg/kg bw) it is suggested to consider the worst case LD50 value of 65.5 mg/kg.


Studies referred to in the expert judgement:




















 Experiment Number Study Type Report conclusion
JPh 1992 Acute oral toxicity study in rats

 LD50 males = 113 mg/kg bw
LD50 females = 65.5 mg/kg bw
LD50 males / females = 85.6 mg/kg bw


 Internal communication Acute oral toxicity study in rats LD50 = 129.9 mg/kg

T001624 is to be classified as toxic if swallowed (Category 3) based on the Janssen expert statement.

Justification for classification or non-classification

Acute oral toxicity


Based on the results of the acute oral toxicity studies, the LD50 of 65.5 mg/kg bw is considered. According to the criteria laid down in Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures, T001624 should be classified as Category 3.